ORGANIC LETTERS
Silver-Catalyzed Vinylogous Fluorination of Vinyl Diazoacetates
2013 Vol. 15, No. 24 6152–6154
Changming Qin and Huw M. L. Davies* Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States
[email protected] Received October 21, 2013
ABSTRACT
A silver-catalyzed vinylogous fluorination of vinyl diazoacetates to generate γ-fluoro-r,β-unsaturated carbonyls is presented. Application of this method to the fluorination of farnesol and steroid derivatives was achieved.
The development of new methods for achieving selective fluorination is a current research area of intense interest.1 Organofluorine compounds display broad utility as valuable pharmaceuticals, agrochemicals, materials and tracers for positron emission tomography.2 γ-Fluoro-R,β-unsaturated carbonyls represent a versatile class of intermediates in organic synthesis and are prevalent motifs in biologically (1) For recent leading reviews, see: (a) Liang, T.; Neumann, C.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52, 8214. (b) Liu, G. Org. Biomol. Chem. 2012, 10, 6243. (c) Hollingworth, C.; Gouverneur, V. Chem. Commun. 2012, 48, 2929. (d) Furuya, T.; Kamlet, A. S.; Ritter, T. Nature 2011, 473, 470. (e) Grushin, V. V. Acc. Chem. Res. 2010, 43, 160. (f) Furuya, T.; Klein, J. E. M. N.; Ritter, T. Synthesis 2010, 11, 1804. For recent examples of fluorination, see: (g) Mazzotti, A. R.; Campbell, M. G.; Tang, P.; Murphy, J. M.; Ritter, T. J. Am. Chem. Soc. 2013, 135, 14012. (h) Sladojevich, F.; Arlow, S. I.; Tang, P.; Ritter, T. J. Am. Chem. Soc. 2013, 135, 2470. (i) Braun, M. G.; Doyle, A. G. J. Am. Chem. Soc. 2013, 135, 12990. (j) Braun, M. G.; Katcher, M. H.; Doyle, A. G. Chem. Sci. 2013, 4, 1216. (k) Shunatona, H. P.; Fruh, N.; Wang, Y.; Rauniyar, V.; Toste, F. D. Angew. Chem., Int. Ed. 2013, 52, 1. (l) Li, Z.; Song, L.; Li, C. J. Am. Chem. Soc. 2013, 135, 4640. (m) Truong, T.; Kilmovica, k.; Daugulis, O. J. Am. Chem. Soc. 2013, 135, 9342. (n) Zhang, Z.; Wang, F.; Mu, X.; Chen, P.; Liu, G. Angew. Chem., Int. Ed. 2013, 52, 7549. (o) Liu, W.; Groves, J. T. Angew. Chem., Int. Ed. 2013, 52, 6024. (p) Fier, P. S.; Luo, J.; Hartwig, J. F. J. Am. Chem. Soc. 2013, 135, 2552. (q) Ye, Y.; Sanford, M. S. J. Am. Chem. Soc. 2013, 135, 4648. (r) Xue, C.; Jiang, X.; Fu, C.; Ma, S. Chem. Commun. 2013, 49, 5651. (s) Liu, W.; Huang, X.; Cheng, M.; Nielsen, R. J.; Goddard, W. A., III; Groves, J. T. Science 2012, 337, 1322. (t) Barker, T. J.; Boger, D. L. J. Am. Chem. Soc. 2012, 134, 13588. (u) Topczewski, J. J.; Tewson, T. J.; Nguyen, H. M. J. Am. Chem. Soc. 2011, 133, 19318. (v) Katcher, M. H.; Sha, A.; Doyle, A. G. J. Am. Chem. Soc. 2011, 133, 15902. (w) Lee, E.; Kamlet, A. S.; Powers, D. C.; Neumann, C. N.; Boursalian, G. B.; Furuya, T.; Choi, D. C.; Hooker, J. M.; Ritter, T. Science 2011, 334, 639. (x) Katcher, M. H.; Doyle, A. G. J. Am. Chem. Soc. 2010, 132, 17402. (y) Tang, P.; Furuya, T.; Ritter, T. J. Am. Chem. Soc. 2010, 132, 12150. (z) Watson, D. A.; Su, M. J.; Teverovskiy, G.; Zhang, Y.; Garcia-Fortanet, J.; Kinzel, T.; Buchwald, S. L. Science 2009, 325, 1661. 10.1021/ol403017e r 2013 American Chemical Society Published on Web 11/14/2013
relevant compounds such as steroids, amino acids and metalloprotease inhibitors.3 Traditional approaches for the synthesis of γ-fluoro-R,β-unsaturated carbonyls mainly rely on electrophilic fluorination of conjugated enol ethers4 and Wittig-type reaction of R-fluoro aldehydes or ketones.5 Recently, we6 and others7 have described that metal-stabilized vinylcarbenes derived from vinyl diazoacetates can selectively display electrophilic reactivity at the vinylogous position instead of the carbene site. This type of behavior is especially favorable when silver catalysts are (2) (a) Ametamey, S. M.; Honer, M.; Schubiger, P. A. Chem. Rev. 2008, 108, 1501. (b) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359. (c) M€ uller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881. (d) Jeschke, P. ChemBioChem 2004, 5, 570. (e) Phelps, M. E. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 9226. (f) Hougham, G. G.; Cassidy, P. E.; Johns, K.; Davidson, T. Fluoropolymers: Synthesis and Properties; Kluwer Academic: New York, 1999. (g) Banks, R. E., Smart, B. E., Tatlow, J. C., Eds. Organofluorine Chemistry: Principles and Commerical Applications; Plenum Press: New York, 1994. (3) (a) Chen, J.; Zheng, F.; Huang, Y.; Qing, F. J. Org. Chem. 2011, 76, 6525. (b) Fan, S.; He, C.; Zhang, X. Tetrahedron 2010, 66, 5218. (c) Orvieto, F.; Koch, U.; Matassa, V. G.; Muraglia, E. Bioorg. Med. Chem. Lett. 2003, 13, 2745. (d) Yoder, N. C.; Kumar, K. Chem. Soc. Rev. 2002, 31, 335. (e) Takeuchi, Y.; Shiragami, T.; Kimura, K.; Suzuki, E.; Shibata, N. Org. Lett. 1999, 1, 1571. (f) Poulter, C. D.; Dolence, J. M. Tetrahedron 1996, 52, 119. (g) Pikul, S.; Mieling, G. E.; Mieling, K. K.; Solinsky, K. M.; De, B.; Almstead, N. G.; Natchus, M. G. U. S. Patent 6,852,751B2, Feb 8, 2005. (4) (a) Poss, A. J.; Shia, G. A. Tetrahedron Lett. 1995, 36, 4721. (b) Purrington, S. T.; Woodard, D. L.; Cale, N. C. J. Fluorine Chem. 1990, 48, 345. (c) Fleming, L.; Goldhill, J.; Paterson, L. Tetrahedron Lett. 1979, 20, 3205. (5) (a) Jiang, H.; Falcicchio, A.; Jensen, K. L.; Paix~ao, M. W.; Bertelsen, S.; Jørgensen, K. A. J. Am. Chem. Soc. 2009, 131, 7153. (b) Oldendorf, J.; Haufe, G. J. Prakt. Chem. 2000, 342, 52. (c) Davis, F. A.; Kasu, P. V. N.; Sundarababu, G.; Qi, H. J. Org. Chem. 1997, 62, 7546.
used.6c,d,7h In this paper, we report a silver-catalyzed vinylogous fluorination to generate highly functionalized γ-fluoro-R,β-unsaturated carbonyls (eq 1).8
Our fluorination study began with examination of different fluoride sources using the styryl diazoacetate 1 as the model substrate. Among fluoride sources examined, many of the standard nucleophilic sources of fluoride failed to give any fluorinated products (Table 1, entries 1 6), but Deoxo-Fluor and DAST9 can provide the desired product 2 in 44% and 55% yield, respectively (Table 1, entries 7 and 8). The use of triethylamine trihydrogen fluoride10 dramatically improved the yield to 90% (Table 1, entry 9). After determining the effect of different silver salts (Table 1, entries 9 11), we chose silver acetate and triethylamine trihydrogen fluoride in dichloromethane as our standard fluorination conditions. In all of these reactions, the ratio of vinylogous versus carbenoid fluorination is >20/1. Having developed the optimized conditions, the scope of the vinylogous fluorination was examined with a variety of vinyldiazo derivatives. The reaction was found to be quite general as illustrated in Scheme 1. The size of ester group (tert-butyl to methyl) did not affect the efficiency of this reaction, affording the desired products 4a c in high yields (92 94%). A particularly interesting example is the substrate 3d with a substituted allyl ester. The desired product 4d was isolated in 85% yield and no intramolecular cyclopropanation was observed. Moreover, when an amide was used as the acceptor group, the reaction can still afford the desired product 4e in 60% isolated yield. (6) (a) Davies, H. M. L.; Saikali, E.; Clark, T. J.; Chee, E. H. Tetrahedron. Lett. 1990, 31, 6299. (b) Davies, H. M. L.; Hu, B.; Saikaki, E.; Bruzinski, P. R. J. Org. Chem. 1994, 59, 4535. (c) Sevryugina, Y.; Weaver, B.; Hansen, J.; Thompson, J.; Davies, H. M. L.; Petrukina, M. A. Organometallics 2008, 27, 1750. (d) Hansen, J.; Davies, H. M. L. Chem. Sci. 2011, 2, 457. (e) Morton, D.; Dick, A. R.; Ghosh, D.; Davies, H. M. L. Chem. Commun. 2012, 48, 5838. (f) Valette, D.; Lian, Y.; Haydek, J. P.; Hardcastle, K, I.; Davies, H. M. L. Angew. Chem., Int. Ed. 2012, 51, 8636. (g) Smith, A. G.; Davies, H. M. L. J. Am. Chem. Soc. 2012, 134, 18241. (h) Qin, C.; Davies, H. M. L. J. Am. Chem. Soc. 2013, 135, 14516. (7) (a) Wang, X.; Xu, X.; Zavalji, P. Y.; Doyle, M. P. J. Am. Chem. Soc. 2011, 133, 16402. (b) Xu, X.; Zavalij, P. Y.; Hu, W.; Doyle, M. P. J. Org. Chem. 2013, 78, 1583. (c) Qian, Y.; Zavalij, P. J.; Hu, W.; Doyle, M. P. Org. Lett. 2013, 15, 1564. (d) Wang, X.; Abrahams, Q. M.; Zavalij, P. Y.; Doyle, M. P. Angew. Chem., Int. Ed. 2012, 51, 5907. (e) Qian, Y.; Xu, X.; Wang, X.; Zavalij, P. J.; Hu, W.; Doyle, M. P. Angew. Chem., Int. Ed. 2012, 51, 5900. (f) Barluenga, J.; Lonzi, G.; Riesgo, L.; Lopez, L. A.; Tomas, M. J. Am. Chem. Soc. 2010, 132, 13200. (g) Pagar, V. V.; Jadhav, A. M.; Liu, R. S. J. Am. Chem. Soc. 2011, 133, 20728. (h) Yue, Y.; Wang, Y.; Hu, W. Tetrahedron Lett. 2007, 48, 3975. (8) Previous transformations on carbenoid fluorination of diazo compounds have been achieved under acidic conditions: (a) Olah, G. A.; Welch, J. T. Synthesis 1974, 896. (b) Setti, E. L.; Mascaretti, O. A. J. Chem. Soc., Perkin Trans. 1 1988, 2059. (c) Pasceri, R.; Bartrum, H. E.; Hayes, C. J.; Moody, C. J. Chem. Commun. 2012, 48, 12077. (9) (a) Singh, R. P.; Shreeve, J. M. Synthesis 2002, 17, 2561. (b) Middleton, W. J. J. Org. Chem. 1975, 40, 574. (c) Lal, G. S.; Pez, G. P.; Pesaresi, R. J.; Prozonic, F. M. Chem. Commun. 1999, 215. (d) Lal, G. S.; Pez, G. P.; Pesaresi, R. J.; Prozonic, F. M.; Cheng, H. J. Org. Chem. 1999, 64, 7048. (10) (a) Haufe, G. J. Prakt. Chem. 1996, 338, 99. (b) Nelson, T. D.; Crouch, R. D. Synthesis 1996, 1031. Org. Lett., Vol. 15, No. 24, 2013
Table 1. Vinylogous Fluorination Optimizationa
entry
catalyst
fluoride
yieldb (%)
1 2 3 4 5 6 7 8 9 10 11
AgOAc AgOAc AgOAc AgOAc AgOAc AgOAc AgOAc AgOAc AgOAc AgSbF6 AgOTf
TMAF TBAFc TBABF KHF2d Fluolead TASF deoxo-Fluor DAST Et3N 3HF Et3N 3HF Et3N 3HF
